BACKGROUND. RNAi is a powerful tool for dissecting genetic interactions. We have developed technologies to conduct rapid and cost-effective shRNA library screens to identify genetic dependencies in cancer cells. PURPOSE. In this project we will collaborate with other investigators (primarily investigators in the NIH Intramural Program) to enable them to conduct shRNA screens in cancer cell lines. SIGNIFICANT MATERIALS AND METHODS. Pooled shRNA library targeting most annotated human genes. Individual shRNA clones for follow up hit validation and mechanism studies. FY2014 ACCOMPLISHMENT. We have completed two shRNA screens in tow different cancer disease areas.